Cytokines play a critical role in the generation of effective immune responses that have the potential to augment HIV replication. Cytokines that drive cellular immune responses (TH1 type) appear the most critical in controlling HIV in the early stages of infection. The mechanism(s) that influence TH 1 responses in the context of acute or recent HIV infection are poorly understood. This proposal will focus on studies of IL-7 and IL-18 in subjects with acute and recent HIV infection. IL-7 is a cytokine critical for not only T cell development in the thymus but also for potentiation of memory T cell responses. IL-18 is critical in mediating TH 1 immune response through induction of gamma interferon production. Both IL-7 and IL-18 have been shown to modulate HIV replication, which may be most profound in early HIV disease. The aims of this study are to examine the role of IL-7 in stimulating thymopoiesis and in contributing to HIV pathogenesis in acute and recent seroconverters. This will be accomplished by evaluating measures of thymic output (TREC, telomere length, naive cell number, thymic size) in relation to viral and CD4 dynamics and determine how IL-7 can impact HIV infection of naive and memory cells in both peripheral blood and lymph node compartments. The second aim will determine the impact of antiretroviral and immune- based therapeutic intervention (therapeutic vaccines) on dynamics of thymic function. Aim 3 will evaluate the role of IL-18 in stimulating TH1 immune responses and in modulating HIV replication in acute and recent seroconverters. The results of these studies will provide important new insights into the earliest immune pathogenic changes of HIV infection and will help focus efforts on developing novel therapeutic strategies.